Discovery, affinity maturation and multimerization of small molecule ligands against human tyrosinase and tyrosinase-related protein 1
OPEN ACCESS
Loading...
Author / Producer
Date
2021-03
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
Human tyrosinase (hTYR) and tyrosinase-related protein 1 (hTYRP1) are closely-related enzymes involved in the synthesis of melanin, which are selectively expressed in melanocytes and, in a pathological context, in melanoma lesions. We used a previously described tyrosinase inhibitor (Thiamidol™) and DNA-encoded library technology for the discovery of novel hTYR and hTYRP1 ligands, that could be used as vehicles for melanoma targeting. Performing de novo selections with DNA-encoded libraries, we discovered novel ligands capable of binding to both hTYR and hTYRP1. More potent ligands were obtained by multimerizing Thiamidol™ moieties, leading to homotetrameric structures that avidly bound to melanoma cells, as revealed by flow cytometry. These findings suggest that melanoma lesions may, in the future, be targeted not only by monoclonal antibody reagents but also by small organic ligands.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
12 (3)
Pages / Article No.
363 - 369
Publisher
Royal Society of Chemistry
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Organisational unit
03463 - Neri, Dario (ehemalig) / Neri, Dario (former)
08641 - Scheuermann, Jörg (Tit.-Prof.) / Scheuermann, Jörg (Tit.-Prof.)
Notes
Funding
182003 - Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature (SNF)
670603 - Fulfilling Paul Ehrlich’s Dream: therapeutics with activation on demand (EC)
670603 - Fulfilling Paul Ehrlich’s Dream: therapeutics with activation on demand (EC)
Related publications and datasets
Is part of: https://doi.org/10.3929/ethz-b-000483530